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Although the determination of the structural basis of potato virus Y (PVY) coat protein (CP) provides the possibility for CP-based antiviral drug design, the role of many specific residues on CP in regulating virion pathogenicity is largely unknown, and fewer small-molecular drugs have been discovered to act on these potential sites. In this study, a series of derivatives of 2,2-dimethyl-2H-chromene are rationally designed by employing a molecular hybridization strategy. We screen a case of phytovirucide C50 that could form a stable H-bond with Ser¹²⁵ of PVY CP to exert antiviral properties. Ser¹²⁵ is further identified to be crucial for CP-viral RNA (vRNA) interaction, enabling PVY virion assembly. This interaction can be significantly inhibited through competitive binding with compound C50. The study enhances our understanding of anti-PVY drug mechanisms and provides a basis for developing new CP-targeting virus particle assembly inhibitors.

Drosophila species belonging to the virilis group offer a unique opportunity for studying olfactory adaptations necessary for survival within forest ecosystems as many of these species breed within decaying plant vascular tissues. However, the knowledge regarding olfactory preferences within their ecological niche is extremely limited. Here, we focus on Drosophila virilis and identify over 120 distinct odors from a natural slime flux source. We identify lignin as an attractant and a positive oviposition cue for D. virilis. Furthermore, lignin-derived guaiacol is highlighted as a robust attractant for D. virilis. We demonstrate that guaiacol is detected by the DvirOr49b receptor, which exhibits a narrow sensitivity to methylphenols, including o-cresol. D. virilis and D. ezoana, both belonging to the virilis group, exhibit strong attraction to o-cresol. In summary, our research offers a comprehensive analysis of the diverse array of odorants encountered by D. virilis within its natural habitat and their behavioral significance.

Climate change intensifies fires, raising questions about their impacts on plant invasions via changes in soil biota and plant-soil feedback (plants alter soil conditions, changing plant growth and vice-versa). We explored effects of plant-soil feedback and simulated fire (heat) on mutualistic arbuscular mycorrhizal (AM) fungal communities and invasive plant growth. Soils were collected from a dominant native grass (Chionochloa macra) and two invasive hawkweeds (Hieracium lepidulum, Pilosella officinarum) in a New Zealand grassland and then heated. In our experiment, both hawkweeds exhibited greater biomass in Pilosella soils, which also had the highest AM fungal richness. Heat had little effect on plant biomass or AM fungal community composition and richness. Hawkweeds altered AM fungal communities relative to the dominant native grass, and moderate soil heating increased Hieracium growth. Hieracium plants also grew better in Pilosella soils, suggesting the potential for soil-mediated invasional meltdown whereby one invasive species facilitates invasion by another.

The transcription factor CCAAT enhancer binding protein alpha (C/EBPα) is a master regulator of myelopoiesis. CEBPA encodes a long (p42) and a truncated (p30) protein isoform from a single mRNA. Mutations that abnormally enhance expression of p30 are associated with acute myelogenous leukemia (AML). We show by mutational analysis that three highly conserved arginine residues in the p30 C/EBPα N-terminus, previously found to be methylated, are involved in myeloid lineage commitment, progenitor proliferation, and differentiation. The conservative amino acid substitution with lysine that retains the amino acid side chain charge enhanced progenitor proliferation, while a non-conservative substitution with uncharged side chains (alanine, leucine) impaired proliferation and enhanced granulopoiesis. Analysis of protein interactions suggested that arginine methylation of p30 C/EBPα differentially determines interactions with SWI/SNF and MLL complexes. Pharmacological targeting of p30 C/EBPα arginine methylation may have clinical relevance in myeloproliferative and inflammatory diseases, in neutropenia, and in leukemic stem cells.

This study presents a non-equimolar diffusion model to enhance the predictive accuracy of coke degradation kinetics in hydrogen-rich blast furnaces, where elevated water vapor (H₂O) levels are present. The model integrates the unreacted core shrink model with the Maxwell-Stefan equation to delineate the 3D curved surface distribution of H₂O concentration and the effective diffusion coefficient within the coke ash layer. Validated against experimental data, the model demonstrated a significant improvement in accuracy, with a deviation range of 0.77%-3.5%, compared to the 15.61%-18.92% deviation for the traditional unreacted core shrink model. This advancement is crucial for optimizing blast furnace design and operation, supporting the industry's transition toward low-carbon ironmaking. The findings highlight the importance of considering non-equimolar diffusion in the reaction kinetics between coke and H₂O, contributing substantially to the scientific understanding and technological advancement in ironmaking.

Tachykinins are short neuropeptides, such as substance P and neurokinin B, that have been shown to interact with Alzheimer's β-amyloid (Aβ) peptide. Neurokinin A (NKA) is a secreted tachykinin neuropeptide that binds to neurokinin receptors and with an emerging role in the brain-gut axis. NKA shares the brain niche with Aβ; thus, we investigate whether and how NKA and Aβ peptide interact. We have used a combination of computational and experimental biophysics to assess the interaction of both peptides in vitro. Using Phe-to-Trp substitution, we have shown that Phe in the FXGLM signature in NKA is important for such interaction and for the modulation of the Aβ peptide amyloid cascade. Besides, cellular experiments have shown that the NKA-Aβ interaction decreases the Aβ peptide toxicity. Altogether, our work raises the intriguing possibility that NKA balance and the NKA-Aβ peptide interplay are relevant in the aggregation process in Alzheimer's disease.

Pyroptosis, driven by the N-terminal domain of gasdermin proteins (GSDM), promotes antitumor immunity by attracting lymphocytes to the tumor microenvironment (TME). However, current pyroptosis-inducing therapies like drug injections and phototherapy are limited to localized treatments, making them unsuitable for widespread or microscopic metastatic lesions. This study engineered oncolytic M1 viruses (rM1-mGSDME_FL and rM1-mGSDME_NT) to selectively deliver GSDME to tumor cells. These modified viruses enhanced tumor cell death in breast cancer models, suppressed tumor growth, extended survival in mice, and boosted immune cell infiltration, demonstrating significant anticancer potential through pyroptosis induction.

Localization to the endoplasmic reticulum (ER) and subsequent disulfide bond formation are crucial processes governing the biogenesis of secretory pathway proteins in eukaryotes. Hence, comprehending the mechanisms underlying these processes is important. Here, we have engineered firefly luciferase (FLuc) as a tool to detect deficiencies in these processes within mammalian cells. To achieve this, we introduced multiple cysteine substitutions into FLuc and targeted it to the ER. The reporter exhibited FLuc activity in response to defects in protein localization or disulfide bond formation within the ER. Notably, this system exhibited outstanding sensitivity, reproducibility, and convenience in detecting abnormalities in these processes. We applied this system to observe a protein translocation defect induced by an inhibitor of HIV receptor biogenesis. Moreover, utilizing the system, we showed that modulating LMF1 levels dramatically impacted the ER's redox environment, confirming that LMF1 plays some critical role in the redox control of the ER.